Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca2+ sensitivity but not on Ca2+ sparks or BK channels. BMC Physiol 2016 Nov 02;16(1):6
Date
11/04/2016Pubmed ID
27806708Pubmed Central ID
PMC5093982DOI
10.1186/s12899-016-0026-zScopus ID
2-s2.0-84994779566 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
BACKGROUND: In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca2+ sparks activate large-conductance Ca2+-activated K+ (BK) channels leading to lowered SMC [Ca2+]i and vasodilation. Here we investigated whether Ca2+ sparks regulate SMC global [Ca2+]i and diameter in the spiral modiolar artery (SMA) by activating BK channels.
METHODS: SMAs were isolated from adult female gerbils, loaded with the Ca2+-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system. Ca2+ signals and vascular diameter changes were recorded using a laser-scanning confocal imaging system. Effects of various pharmacological agents on Ca2+ signals and vascular diameter were analyzed.
RESULTS: Ca2+ sparks and waves were observed in pressurized SMAs. Inhibition of Ca2+ sparks with ryanodine increased global Ca2+ and constricted SMA at 40 cmH2O but inhibition of Ca2+ sparks with tetracaine or inhibition of BK channels with iberiotoxin at 40 cmH2O did not produce a similar effect. The ryanodine-induced vasoconstriction observed at 40 cmH2O was abolished at 60 cmH2O, consistent with a greater Ca2+-sensitivity of constriction at 40 cmH2O than at 60 cmH2O. When the Ca2+-sensitivity of the SMA was increased by prior application of 1 nM endothelin-1, ryanodine induced a robust vasoconstriction at 60 cmH2O.
CONCLUSIONS: The results suggest that Ca2+ sparks, while present, do not regulate vascular diameter in the SMA by activating BK channels and that the regulation of vascular diameter in the SMA is determined by the Ca2+-sensitivity of constriction.
Author List
Krishnamoorthy G, Reimann K, Wangemann PAuthor
Gayathri K. Natarajan Research Scientist II in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium Signaling
Cochlea
Endothelin-1
Female
Gerbillinae
Large-Conductance Calcium-Activated Potassium Channels
Muscle, Smooth, Vascular
Ryanodine
Vasoconstriction